Blood test would identify harmful protein

By Alyson Ward |
November 23, 2012

Dr. Edward T.H. Yehuses an echo ultrasound machine to view a heart as part of his research.

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Dr. Edward T.H. Yeh leads a team of researchers studying the cardiotoxicity of the chemotherapy drug doxorubicin. The team includes researchers from the University of Texas M.D. Anderson Cancer Center and the Texas Heart Institute at St. Luke s Episcopal Hospital.

Photo By Thomas B. Shea

11/14/12 : Dr. Edward T.H. Yeh, the leader of a research team that has figured out why a common chemotherapy drug (doxorubicin) can do serious, irreversible damage to a patient's heart tissue. In the photo Dr. Yeh uses an Echo Ultrasound machine on Alvin Community College Intern Tim Wong to see if his heart is healthy. Because of the danger of the Chemotherapy to the heart, the heart has an ultrasound done before the first Chemotherapy session and is checked again after a few Chemotherapy sessions. Tim Wong was not sick he was just used as a model for the photograph.

Photo By Thomas B. Shea

11/14/12 : Dr. Edward T.H. Yeh, the leader of a research team that has figured out why a common chemotherapy drug (doxorubicin) can do serious, irreversible damage to a patient's heart tissue. In the photo Dr. Yeh uses an Echo Ultrasound machine on Alvin Community College Intern Tim Wong to see if his heart is healthy. Because of the danger of the Chemotherapy to the heart, the heart has an ultrasound done before the first Chemotherapy session and is checked again after a few Chemotherapy sessions. Tim Wong was not sick he was just used as a model for the photograph.

Some of the most common forms of cancer are often treated with a drug that can cause heart failure. Patients will make it through chemotherapy, then discover the drug that killed their cancer has done irreversible damage to their heart tissue.

But researchers in Houston have made a discovery that could help patients avoid that damage - and their findings might lead to new, safer drugs.

The protein is Topoisomerase2, known as Top2, and it comes in two forms, Top2a and Top2b. Cancer cells have high amounts of Top2a, while normal cells have almost none. Doxorubicin, then, works by binding to Top2a and to DNA, breaking the DNA and making the cancer cell kill itself.

Top2b, meanwhile, is present in normal cells. And in the heart, where there's no Top2a, doxorubicin binds with Top2b and damages normal, healthy heart cells.

The answer, then, may be to remove Top2b from the heart, eliminating the chance for doxorubicin to do its damage, Yeh said.

The protein has no apparent role in the functioning of the heart, he said: "You can take it out and prevent cardiotoxicity and it really doesn't hurt the heart at all."

The technique has been successful already in tests on mice, and eventually it may lead to a new class of chemotherapy drugs, Yeh said.

But in the meantime, the researchers' discovery can help patients in a more immediate way: Now that we know about Top2b, we can identify which patients are likely to develop heart damage from taking doxorubicin.

"We can actually use this protein to develop a blood test," Yeh said.

If patients have a high level of Top2b, they'll be more sensitive to the chemotherapy drug. For those patients, doctors can then prescribe different medications.

"By knowing whether you're sensitive or resistant to doxorubicin, you can have different strategies to deal with that," Yeh said.

The team is conducting a clinical study now, he said, and has tried the blood test on about 20 patients.

"The difference is like day and night," Yeh said. "You can clearly see that a patient who is sensitive (to doxorubicin) will have a much higher amount (of Top2b)."

The team plans to recommend that all patients be tested before they take doxorubicin.